The overall goal of this work is to establish new criteria to differentiate acute Irritant Contact Dermatitis (ICD) from Allergic Contact Dermatitis (ACD) by using a video rate (real-time), near-infrared confocal reflectance microscope (CM). The specific aims are (I) to optimize a video-rate CM for imaging, characterizing and distinguishing acute allergic and irritant contact dermatitis in vivo; (ii) to investigate the kinetic changes of both forms of CD using this non-invasive imaging technique in order to determine their characteristic features versus time to better understand their pathogenesis; and (iii) to measure the sensitivity of patch testing enhanced by non-invasive CM evaluation. Contact Dermatitis affects approximately 20 percent of the population in the US, and is the most common form of occupational dermatosis. It is divided mechanistically into ICD and ACD. The ICD is produced by the toxic effect of certain chemicals on the skin while ACD is induced by a delayed hypersensitivity response of the host to an antigenic chemical. The latter form is characterized by a cascade of immunologic events that occurs mostly in the superficial layers of the skin. Morphologic features of both forms of CD, however, are very similar on gross and microscopic examination and it is difficult to differentiate one from the other. Our real-time CM has been used effectively to non-invasively image normal and diseased skin in vivo. Using near-infrared laser and water immersion objective lenses (NA=0.7-1.2), images can be obtained at high lateral (<1.0 micron) and transverse (virtual section thickness) resolutions down to a depth of 300-400 microns. The use of a non-invasive CM for evaluating the stages of allergic and irritant skin reactions in vivo, as well as to enhance patch testing, may help physicians to improve their diagnostic skills in this area, and may help to have a better understanding of the pathogenesis of these inflammatory skin conditions. The lack of artifacts from conventional histology gives a more realistic picture of pathophysiology. We also expect that our results may ultimately translate into more rational and effective care for patients with this common and frequently disabling problem.